Simultaneous proteosome inhibition and heat shock protein induction by bortezomib is beneficial in experimental pancreatitis

• Published in: European journal of pharmacology Vol. 616; no. 1; pp. 270 - 274
• Main Authors: Szabolcs, Annamária, Biczó, György, Rakonczay, Zoltán, Tiszlavicz, László, Halm, Gabriella, Wittmann, Tibor, Takács, Tamás
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.08.2009; Elsevier
• Subjects: Acute pancreatitis; Animals; Biological and medical sciences; Boronic Acids - pharmacology; Boronic Acids - therapeutic use; Bortezomib; CCK-8; Gastroenterology. Liver. Pancreas. Abdomen; Heat-Shock Proteins - metabolism; HSP; I-κB; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Multienzyme Complexes - antagonists & inhibitors; NF-κB; Other diseases. Semiology; Pancreas - drug effects; Pancreas - metabolism; Pancreas - pathology; Pancreatitis - drug therapy; Pancreatitis - enzymology; Pancreatitis - metabolism; Pancreatitis - pathology; Pharmacology. Drug treatments; Protease Inhibitors - pharmacology; Protease Inhibitors - therapeutic use; Pyrazines - pharmacology; Pyrazines - therapeutic use; Rats; Rats, Wistar; NF-κB; CCK-8; Acute pancreatitis; Bortezomib; HSP; I-κB; Antineoplastic agent; Induction; Acute; Pancreatitis; Neuropeptide; Analog; Proteasome inhibitor; Heat shock protein; Dipeptides; Digestive diseases; Cholecystokinin; Transcription factor NFκB; Pancreatic disease
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2009.05.019

The proteosome inhibitor bortezomib is used in the treatment of patients with multiple myeloma. Proteosomes are responsible for the degradation of I-κB, the inhibitory protein of transcription factor nuclear factor kappa B (Nf-κB). The heat shock protein (HSP) inducing effect of bortezomib is also documented. The aim of our work was to test the anti-inflammatory effect of bortezomib in cholecystokinin-octapeptide (CCK-8)-induced acute pancreatitis. Male Wistar rats were divided into three groups ( n = 8 in each). Group P received an i.p. injection of physiological saline (p.s.) 60 min. before the induction of acute pancreatitis by three hourly s.c. injections of 100 µg/kg CCK-8. Group BP received 1 mg/kg bortezomib dissolved in p.s. 1 h previous to pancreatitis induction. Group C was treated with the vehicle (p.s.). Animals were exsanguinated 4 h after the last injection of CCK-8. Bortezomib pre-treatment significantly reduced the pancreatic weight/body weight ratio, and improved the histology by decreasing the extent of vacuolization and infiltration. Bortezomib pre-treatment inhibited I-κBβ degradation, and induced the synthesis of HSP72. The results confirmed the anti-inflammatory effect of bortezomib in acute experimental pancreatitis. This effect of the drug is presumably mediated by the inhibition of Nf-κB activation and induction of HSP synthesis.